Docosahexaenoic acid reduces GABA response in substantia nigra neuron of rat

1. The effects of docosahexaenoic acid (DHA) on gamma-aminobutyric acid (GABA) response (I-GABA) were investigated on the neuron acutely dissociated from fat substantia nigra (SN), with the use of patch recordings in a whole cell mode. 2. DHA (5 x 10(-6) M) reduced bicuculline-sensitive GABA (10(-4) M) current by 50.3 +/- 13.1% (mean +/- SE) at a fielding potential (V-h) Of -40 mV under voltage clamp. 3. The GABA concentrations for the half-maximum and threshold of I-GABA were not altered by the presence or absence of 5 x 10(-6) M DHA in the external solution. 4. The decrease of 10(-4) M I-GABA, following the peak during GABA application, was more rapid in the presence of 5 x 10 M DHA than in its absence. The time constants for I-GABA decay were significantly different between the two conditions. 5. DHA reduced the I-GABA and the glycine-induced response (I-gly) in a concentration-dependent manner. On the contrary, DHA potentiated the aspartate-induced response (I-asp) in a concentration-dependent manner, suggesting that DHA influences the activity of chloride channels but does not exhibit a nonspecific blocking effect on any ionic channel. 6. The application of thimerosal did not affect the reduction of I-GABA by DHA, suggesting it unlikely that DHA reduces the I-GABA by binding to phospholipids or triglycerides and altering the lipid environment around the chloride channel. 7. Arachidonic acid (AA) also reduced the I-GABA in a manner similar to DHA. Docosapentaenoic acid (DPA) reduced the I-GABA less potently than DHA. Other polyunsaturated and saturated fatty acids, such as docosatrienoic acid, docosatetraenoic acid, palmitic acid, and oleic acid, had very little or no effect on the I-GABA. 8. DHA, as well as AA, may play an important role in modulating neuronal excitability by reducing the I-GABA and I-gly, and potentiating N-methyl-D-aspartate receptor-mediated responses in the SN.